US4634708AExpiredUtility

Indolophenanthridines useful as dopaminergic and analgesic agents

Assignee: SANDOZ LTDPriority: Jan 25, 1984Filed: Jan 25, 1985Granted: Jan 6, 1987
Est. expiryJan 25, 2004(expired)· nominal 20-yr term from priority
A61P 9/00A61P 37/04A61P 9/12A61P 25/00A61P 25/04A61P 13/02A61P 15/00C07D 457/14C07D 209/90
55
PatentIndex Score
11
Cited by
4
References
17
Claims

Abstract

4,6,6a,7,8,12b-hexahydro-indolo[4,3-ab]phenanthridines are useful as dopaminergic and analgesic agents.

Claims

exact text as granted — not AI-modified
What we claim is: 
     
       1. A compound of formula I ##STR16## wherein R 1  and R 3  independently are hydrogen, (C 1-4 )alkyl, (C 3-5 )alkenyl wherein the double bond is not adjacent to the nitrogen atom, (C 3-6 )cycloalkyl(C 1-3 )alkyl, phenyl(C 1-3 )alkyl optionally substituted in the phenyl ring by (C 1-4 )alkyl, (C 1-4 )alkoxy, hydroxy or halogen, or 2- or 3-furyl(C 1-3 )alkyl, R 2  is hydrogen, chlorine, bromine or methyl,   X 1  and X 2  independently are hydrogen, (C 1-4 )alkyl, (C 1-4 )alkoxy, hydroxy, halogen or trifluoromethyl, in free base or acid addition salt form.     
     
     
       2. A compound of claim 1 wherein R 1  and R 3  independently are hydrogen, (C 1-4 )alkyl, (C 3-5 )alkenyl wherein the double bond is not adjacent to the nitrogen atom, (C 3-6 )cycloalkyy (C 1-3 )alkyl, phenyl(C 1-3 )alkyl optionally monosubstituted by methyl, methoxy, hydroxy or halogen, or 2- or 3-furyl(C 1-3 )alkyl,   R 2  is hydrogen, chlorine, bromine or methyl,   X 1  and X 2  independently are hydrogen, (C 1-4 )alkyl, (C 1-4 )alkoxy, hydroxy, halogen or trifluormethyl.   
     
     
       3. A compound of claim 1 wherein R 1  is hydrogen or (C 1-4 )alkyl,   R 2  is hydrogen, chlorine, bromine or methyl,   R 3  is hydrogen, (C 1-4 )alkyl, benzyl optionally monosubstituted by (C 1-4 )alkoxy, or 2-furylmethyl,   X 1  is in position 10, 11 or 12 and is hydrogen, (C 1-4 )alkyl, (C 1-4 )alkoxy, hydroxy, halogen or trifluoromethyl and   X 2  is hydrogen.   
     
     
       4. A compound of claim 1 wherein R 1 , R 2 , X 1  and X 2  are hydrogen and R 3  is methyl, in form of the (-)-isomer. 
     
     
       5. A pharmaceutical composition useful in the treatment of Parkinson's disease, conjective cardiac insufficiency, hypertension, renal failure with reduced urine excretion or pain comprising a therapeutically effective amount of a compound according to claim 1 in pharmaceutically acceptable form, in association with a pharmaceutical carrier or diluent. 
     
     
       6. A method of treating a subject suffering from Parkinson's disease, congestive cardiac insufficiency, hypertension, renal failure with reduced urine excretion or pain, which comprises administering a therapeutically effective amount of a compound of claim 1 in pharmaceutically acceptable form. 
     
     
       7. The compound of claim 1, which is trans-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo[4,3-ab] phenanthridine. 
     
     
       8. A compound of claim 1 in which R 2  is hydrogen and R 1 , X 1 , X 2 , and R 3  are respectively:   ______________________________________                                    
(a)    H         H      H    CH.sub.2CH.sub.3                             
(b)    H         H      H    CH.sub.2CH.sub.2CH.sub.3                     
(c)    CH.sub.3  H      H    CH.sub.3                                     
(d)    H         H      H    CH.sub.2CHCH.sub.2                           
(e)    H         H      H                                                 
                              ##STR17##                                   
(f)    H         H      H                                                 
                              ##STR18##                                   
______________________________________                                    
     
     
     
       9. A compound of claim 1 in which R 2  is hydrogen and R 1 , X 1 , X 2  and R 3  are respectively:   ______________________________________                                    
(g)     H         11-OCH.sub.3                                            
                             H     --CH.sub.3                             
(h)     H         11-OH      H     --CH.sub.3                             
(i)     H         10-OCH.sub.3                                            
                             H     --CH.sub.3                             
(j)     H         10-OH      H     --CH.sub.3                             
(k)     H         10-CH.sub.3                                             
                             H     --CH.sub.3                             
(l)     H         11-CH.sub.3                                             
                             H     --CH.sub.3                             
(m)     H         10-CF.sub.3                                             
                             H     --CH.sub.3                             
(n)     H         10-CH.sub.3                                             
                             12-CH.sub.3                                  
                                   --CH.sub.3                             
(o)     H         11-Cl      H     --CH.sub.3                             
(p)     H         12-OH      H     --CH.sub.3                             
______________________________________                                    
     
     
     
       10. The compound of claim 1 which is (+)-trans- 4,6,6a,7,8,12b-hexahydro-7-methyl-indolo[4,3-ab]phenanthridine. 
     
     
       11. The compound of claim 1 which is trans-4,6,6a,7,8,12b-hexahydroindolo[4,3-ab]-phenanthridine. 
     
     
       12. The compound of claim 1 in which R 1  is hydrogen R 2 , X 1  , X 2  and R 3  are H,11-OCH 3 , H, and H in racemate form. 
     
     
       13. The compound of claim 1 in which R 1  is hydrogen and R 2 , X 1 , X 2  and R 3  are H, H, H, and H in (-) isomer form. 
     
     
       14. The compound of claim 1 which is trans-4,6,6a,7,8,12b-hexahydro-4,7-dimethyl-indolo[4,3-ab]phenanthridine. 
     
     
       15. The compound of claim 1 in which trans-5-bromo-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo[4,3-ab]phenanthridine. 
     
     
       16. The compound of claim 1 in racemate form in which R 1 , R 2 , R 3 , X 1  and X 2  are respectively:   ______________________________________                                    
(a)    H         Cl      --CH.sub.3                                       
                                   H   H                                  
(b)    H         --CH.sub.3                                               
                         --CH.sub.3                                       
                                   H   H                                  
______________________________________                                    
     
     
     
       17. The compound of claim 1 in (-) isomer form in which R 1 , R 2 , R 3 , X 1  and X 2  are respectively:   ______________________________________                                    
(c)    H         Br      --CH.sub.3                                       
                                   H   H                                  
(d)    H         --CH.sub.3                                               
                         --CH.sub.3                                       
                                   H   H                                  
______________________________________

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